Incidental Mutation 'R0361:Cgas'
ID 30112
Institutional Source Beutler Lab
Gene Symbol Cgas
Ensembl Gene ENSMUSG00000032344
Gene Name cyclic GMP-AMP synthase
Synonyms Mb21d1, E330016A19Rik
MMRRC Submission 038567-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.159) question?
Stock # R0361 (G1)
Quality Score 199
Status Validated
Chromosome 9
Chromosomal Location 78337808-78350519 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 78340534 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Lysine to Asparagine at position 399 (K399N)
Ref Sequence ENSEMBL: ENSMUSP00000063331 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034898] [ENSMUST00000070742]
AlphaFold Q8C6L5
PDB Structure Structure of cyclic GMP-AMP Synthase (cGAS) [X-RAY DIFFRACTION]
Structure of Binary Complex of cGAS with Bound dsDNA [X-RAY DIFFRACTION]
Structure of Ternary Complex of cGAS with dsDNA and Bound ATP [X-RAY DIFFRACTION]
Structure of Ternary Complex of cGAS with dsDNA and Bound 5 -pppG(2 ,5 )pG [X-RAY DIFFRACTION]
Structure of Ternary Complex of cGAS with dsDNA and Bound 5 -pppdG(2 ,5 )pdG [X-RAY DIFFRACTION]
Structure of Ternary Complex of cGAS with dsDNA and Bound 5 -pG(2 ,5 )pA [X-RAY DIFFRACTION]
Structure of Ternary Complex of cGAS with dsDNA and Bound c[G(2 ,5 )pA(3 ,5 )p] [X-RAY DIFFRACTION]
Structure of mouse cGAS bound to 18 bp DNA [X-RAY DIFFRACTION]
Structure of mouse cGAS bound to an 18bp DNA and cGAS product [X-RAY DIFFRACTION]
Mouse cyclic GMP-AMP synthase (cGAS) in complex with DNA [X-RAY DIFFRACTION]
Predicted Effect probably benign
Transcript: ENSMUST00000034898
SMART Domains Protein: ENSMUSP00000034898
Gene: ENSMUSG00000032344

DomainStartEndE-ValueType
low complexity region 8 23 N/A INTRINSIC
low complexity region 148 163 N/A INTRINSIC
Mab-21 199 394 1.89e-6 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000070742
AA Change: K399N

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000063331
Gene: ENSMUSG00000032344
AA Change: K399N

DomainStartEndE-ValueType
low complexity region 8 23 N/A INTRINSIC
low complexity region 148 163 N/A INTRINSIC
Mab-21 199 498 2.79e-91 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000127190
SMART Domains Protein: ENSMUSP00000114277
Gene: ENSMUSG00000032344

DomainStartEndE-ValueType
low complexity region 84 99 N/A INTRINSIC
Pfam:Mab-21 136 229 6.8e-16 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000128935
Predicted Effect noncoding transcript
Transcript: ENSMUST00000129983
Predicted Effect noncoding transcript
Transcript: ENSMUST00000144982
Meta Mutation Damage Score 0.4727 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.2%
  • 10x: 96.0%
  • 20x: 91.7%
Validation Efficiency 100% (1/1)
MGI Phenotype FUNCTION: The protein encoded by this gene is a DNA binding cytosolic protein that catalyzes the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) after sensing the presence of DNA in the cytoplasm. cGAMP binds another protein, Stimulator of interferon genes (STING), leading to the induction of interferons, and a host immune response. Reduced expression of this gene inhibits interferon induction in the presence of some viral infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
PHENOTYPE: Mice homozygous for a null allele exhibit increased susceptibility to viral infection and abnormal innate immunity. [provided by MGI curators]
Allele List at MGI

All alleles(6) : Targeted(2) Gene trapped(4)
Other mutations in this stock
Total: 77 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700006A11Rik T G 3: 124,207,283 (GRCm39) T303P possibly damaging Het
1700010I14Rik G T 17: 9,211,378 (GRCm39) V176L probably benign Het
1700034J05Rik T C 6: 146,853,869 (GRCm39) T262A possibly damaging Het
Adgrl3 A T 5: 81,908,544 (GRCm39) I1165F probably damaging Het
Ankhd1 T C 18: 36,780,267 (GRCm39) I1773T probably damaging Het
Api5 A T 2: 94,253,842 (GRCm39) L287* probably null Het
Apol10b A T 15: 77,469,586 (GRCm39) M197K possibly damaging Het
Bcl2 G A 1: 106,640,424 (GRCm39) R63W probably damaging Het
Cacna1h A G 17: 25,608,396 (GRCm39) M731T probably damaging Het
Cav1 C A 6: 17,339,352 (GRCm39) R146S possibly damaging Het
Cdhr2 A T 13: 54,881,820 (GRCm39) I1118F probably damaging Het
Cdk7 A T 13: 100,848,062 (GRCm39) Y153* probably null Het
Cemip A G 7: 83,613,218 (GRCm39) I660T probably benign Het
Cfap65 A T 1: 74,964,599 (GRCm39) L518Q probably damaging Het
Cngb3 A G 4: 19,366,467 (GRCm39) H176R probably benign Het
Cstdc4 T C 16: 36,004,648 (GRCm39) S7P probably damaging Het
Cux1 T A 5: 136,308,351 (GRCm39) I1263F probably damaging Het
Dnajc13 A G 9: 104,044,258 (GRCm39) M1867T probably benign Het
Dock2 A G 11: 34,388,327 (GRCm39) L202P probably damaging Het
Dyrk3 A G 1: 131,057,769 (GRCm39) S100P probably benign Het
Efr3b A T 12: 4,027,923 (GRCm39) S376T probably benign Het
Eps8l2 A C 7: 140,936,112 (GRCm39) N222T probably benign Het
Ermp1 A T 19: 29,608,806 (GRCm39) Y158N probably damaging Het
Fam13a A G 6: 58,964,159 (GRCm39) V91A probably benign Het
Fat3 A G 9: 15,909,699 (GRCm39) V2101A possibly damaging Het
Fsip2 T C 2: 82,805,849 (GRCm39) S723P possibly damaging Het
Garem1 G T 18: 21,432,801 (GRCm39) C9* probably null Het
Gdpd5 A G 7: 99,107,997 (GRCm39) I530V possibly damaging Het
Gm15217 T A 14: 46,617,841 (GRCm39) probably benign Het
Gm4922 T C 10: 18,659,289 (GRCm39) T478A probably benign Het
H2-M5 A G 17: 37,298,328 (GRCm39) I329T possibly damaging Het
Ing4 G A 6: 125,024,857 (GRCm39) C200Y probably damaging Het
Kcnip1 A T 11: 33,793,177 (GRCm39) M5K probably benign Het
Kdsr T C 1: 106,675,517 (GRCm39) E102G probably damaging Het
Krt15 C T 11: 100,024,007 (GRCm39) V346M probably benign Het
Lgr6 C T 1: 134,921,748 (GRCm39) A199T probably damaging Het
Lrrc55 A T 2: 85,026,589 (GRCm39) M145K probably damaging Het
Lrrtm2 A G 18: 35,345,985 (GRCm39) I439T probably benign Het
Map2k6 T C 11: 110,390,335 (GRCm39) F290L probably damaging Het
Me1 T A 9: 86,533,055 (GRCm39) I136F probably damaging Het
Mfap2 A G 4: 140,742,294 (GRCm39) D98G probably damaging Het
Mfsd13a C T 19: 46,354,943 (GRCm39) T40I probably benign Het
Mst1 T C 9: 107,962,096 (GRCm39) F696L probably damaging Het
Mta1 A G 12: 113,096,961 (GRCm39) probably null Het
Myh15 A T 16: 48,934,368 (GRCm39) N645I probably benign Het
Myo7b T A 18: 32,147,262 (GRCm39) I94F probably damaging Het
Nefh A T 11: 4,890,799 (GRCm39) S607T probably benign Het
Noa1 G A 5: 77,445,020 (GRCm39) Q600* probably null Het
Nr2f2 A G 7: 70,007,810 (GRCm39) V71A possibly damaging Het
Oas2 A T 5: 120,876,466 (GRCm39) F492L probably damaging Het
Olfm3 T A 3: 114,914,622 (GRCm39) D211E probably damaging Het
Or2y17 A T 11: 49,231,641 (GRCm39) Y94F probably benign Het
Osmr A G 15: 6,871,432 (GRCm39) probably null Het
Plagl2 A T 2: 153,073,523 (GRCm39) D459E probably benign Het
Plch2 T C 4: 155,091,168 (GRCm39) D148G possibly damaging Het
Plxnc1 C A 10: 94,700,869 (GRCm39) C605F probably damaging Het
Ppm1m T C 9: 106,075,325 (GRCm39) E108G probably damaging Het
Prr14l A C 5: 32,950,985 (GRCm39) L1936R probably damaging Het
Ralgapa1 A G 12: 55,723,354 (GRCm39) I1771T possibly damaging Het
Rhobtb2 T C 14: 70,033,357 (GRCm39) T538A probably benign Het
Rictor A G 15: 6,813,588 (GRCm39) N1025D possibly damaging Het
Sec23a T G 12: 59,037,804 (GRCm39) D324A probably damaging Het
Srgap1 A T 10: 121,883,097 (GRCm39) M1K probably null Het
Syne2 T A 12: 75,965,384 (GRCm39) F801I probably benign Het
Synrg T A 11: 83,915,163 (GRCm39) probably null Het
Tas2r140 T G 6: 40,468,232 (GRCm39) F21V probably benign Het
Tmem260 A T 14: 48,689,504 (GRCm39) T108S possibly damaging Het
Trim2 T C 3: 84,098,083 (GRCm39) Y406C probably damaging Het
Ttn T C 2: 76,673,746 (GRCm39) probably benign Het
Vmn1r53 A T 6: 90,201,064 (GRCm39) S87T possibly damaging Het
Vmn2r115 T A 17: 23,564,196 (GRCm39) Y123N probably benign Het
Vmn2r28 T A 7: 5,496,715 (GRCm39) I46F probably benign Het
Zan T C 5: 137,395,028 (GRCm39) T4381A unknown Het
Zfp457 A G 13: 67,440,710 (GRCm39) F622L probably damaging Het
Zfp994 A T 17: 22,419,091 (GRCm39) N619K probably benign Het
Zfy1 T C Y: 726,121 (GRCm39) H548R possibly damaging Het
Zmym4 A T 4: 126,804,938 (GRCm39) S441T probably benign Het
Other mutations in Cgas
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00501:Cgas APN 9 78,342,869 (GRCm39) missense probably damaging 1.00
IGL00727:Cgas APN 9 78,342,770 (GRCm39) missense probably damaging 0.99
IGL00730:Cgas APN 9 78,342,770 (GRCm39) missense probably damaging 0.99
IGL00731:Cgas APN 9 78,342,770 (GRCm39) missense probably damaging 0.99
IGL00737:Cgas APN 9 78,342,770 (GRCm39) missense probably damaging 0.99
IGL00753:Cgas APN 9 78,342,770 (GRCm39) missense probably damaging 0.99
IGL00754:Cgas APN 9 78,342,770 (GRCm39) missense probably damaging 0.99
IGL00832:Cgas APN 9 78,341,599 (GRCm39) missense probably damaging 1.00
IGL00848:Cgas APN 9 78,342,770 (GRCm39) missense probably damaging 0.99
IGL00849:Cgas APN 9 78,342,770 (GRCm39) missense probably damaging 0.99
IGL01627:Cgas APN 9 78,349,996 (GRCm39) missense possibly damaging 0.70
IGL01642:Cgas APN 9 78,344,680 (GRCm39) missense probably damaging 1.00
IGL01993:Cgas APN 9 78,349,802 (GRCm39) missense probably benign 0.18
IGL02206:Cgas APN 9 78,350,362 (GRCm39) splice site probably null
IGL02367:Cgas APN 9 78,341,667 (GRCm39) missense probably benign 0.04
IGL03053:Cgas APN 9 78,344,719 (GRCm39) missense probably benign 0.14
R0426:Cgas UTSW 9 78,343,020 (GRCm39) splice site probably benign
R1531:Cgas UTSW 9 78,349,763 (GRCm39) missense probably damaging 1.00
R1554:Cgas UTSW 9 78,342,838 (GRCm39) missense probably damaging 1.00
R1817:Cgas UTSW 9 78,341,593 (GRCm39) critical splice donor site probably null
R1872:Cgas UTSW 9 78,340,484 (GRCm39) missense probably benign 0.06
R1964:Cgas UTSW 9 78,344,737 (GRCm39) missense probably damaging 0.99
R4162:Cgas UTSW 9 78,341,686 (GRCm39) missense probably damaging 1.00
R6951:Cgas UTSW 9 78,349,840 (GRCm39) missense probably damaging 1.00
R7199:Cgas UTSW 9 78,340,315 (GRCm39) missense probably benign 0.19
R8798:Cgas UTSW 9 78,350,348 (GRCm39) missense probably benign
R9025:Cgas UTSW 9 78,349,787 (GRCm39) missense probably benign 0.03
Predicted Primers PCR Primer
(F):5'- GAGGCACTCAAGAAAGAATGCTAACAAC -3'
(R):5'- CCACACTTGAAATACACTAAGTGGGTCA -3'

Sequencing Primer
(F):5'- TGCTAACAACTTATCGAAGCAGG -3'
(R):5'- gaggcagagcagagttagg -3'
Phenotypic Description

The mutation is an A to T transversion (sense strand) at base pair 78433252 (v38) on chromosome 9 in the GenBank genomic region NC_000075 encoding Mb21d1 (alternatively, E330016A19Rik or cGAS). The mutation corresponds to residue 1266 in the NM_173386 mRNA sequence and 1197 in the ENSMUST00000070742 cDNA sequence in exon 5 of 5 total exons.

1246 TGCAGAAAAGAATGTTTAAAATTAATGAAATACCTTTTG

393  -C--R--K--E--C--L--K--L--M--K--Y--L--L-

The mutated nucleotide is indicated in red. The mutation results in a lysine (K) to asparagine (N) substitution at amino acid residue 399.
Genotyping
Genomic DNA sequencing trace. Chr. + strand shown.

R0361:Mb21d1 (cGAS) genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide change.

Primers

R03610075_(F): 5’-GAGGCACTCAAGAAAGAATGCTAACAAC -3’

R03610075_(R): 5’- CCACACTTGAAATACACTAAGTGGGTCA -3’

Primers for sequencing

R03610075_seq(F1): 5’- TGCTAACAACTTATCGAAGCAGG -3'

R03610075_seq(R1): 5’- GAGGCAGAGCAGAGTTAGG -3’

PCR program

1) 95°C             2:00

2) 95°C             0:30

3) 56°C             0:30

4) 72°C             1:00

5) repeat steps (2-4) 29X

6) 72°C             7:00

7)  4°C              ∞

The following sequence of 829 nucleotides is amplified (Chr. 9:78433069-78433897, Chr. + strand):

gaggcactca agaaagaatg ctaacaactt atcgaagcag gagctgaggt tcctggggtc

ccactgactg tcctgcgggt cctgggtcca catgtgaaag atggcagttt tcacatggta

ggaacagaat gcatccagct cttgaaactc ttttttcaac tgttccaaaa ggtatttcat

taattttaaa cattcttttc tgttaaataa gaaagaagat actcattttt acttacttac

aactgtctct tttgagacag ggtctctcta tgtaaccctg gctttcctgg gacacaagag

atccacccgt ccctgtttcc caagaacaag tgctggaatt aaagatgtgc gccaccttgt

ctgtctcttt ttctttttta aacatacttt cttcttttct tccaattttt taaggcaggg

tctcattagc tcaggttggc cataaactca tcatgtagca ggggctggcc tttggctcct

aactctgctc tgcctctcaa gtgctaggaa tagtgtacac taccatactt gggtcaatgc

cacttccttt tttttaattt attttttaaa tttttaaaaa tttaaaaaaa aattttaaag

attttcttta ttattatatg taagtacact gtagctgtct tcagacaccc cagaagaggg

catcagatct cattatggat agttgtggtt gctaggattt gaactcagga ccttcggaag

aacagtcagt gctcttaacc actgagccat ctctaggccc ccattgtcac ttcttaatgg

tgtatattct aggaagaaaa atgacccact tagtgtattt caagtgtgg

Primer binding sites are underlined; sequencing primer binding site is highlighted in gray; the mutated nucleotide is indicated in red (T>A, Chr. + strand; A>T, sense strand).
Posted On 2013-04-24